Interleukin-32: A new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis

Moschen, Alexander R., Fritz, Teresa Fritz, Clouston, Andrew D., Rebhan, Ilka, Bauhofer, Oliver, Barrie, Helen D., Powell, Elizabeth E., Kim, Soo-Hyun, Dinarello, Charles A., Bartenschlager, Ralf, Jonsson, Julie R. and Tilg, Herbert (2011) Interleukin-32: A new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology, 53 6: 1819-1829. doi:10.1002/hep.24285

Author Moschen, Alexander R.
Fritz, Teresa Fritz
Clouston, Andrew D.
Rebhan, Ilka
Bauhofer, Oliver
Barrie, Helen D.
Powell, Elizabeth E.
Kim, Soo-Hyun
Dinarello, Charles A.
Bartenschlager, Ralf
Jonsson, Julie R.
Tilg, Herbert
Title Interleukin-32: A new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
Publication date 2011-06
Sub-type Article (original research)
DOI 10.1002/hep.24285
Volume 53
Issue 6
Start page 1819
End page 1829
Total pages 11
Place of publication Hoboken, NJ, U.S.A.
Publisher John Wiley & Sons, Inc.
Collection year 2012
Language eng
Formatted abstract
Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. Conclusion: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.

Copyright © 2011 American Association for the Study of Liver Diseases.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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Created: Thu, 11 Aug 2011, 13:52:21 EST by Matthew Lamb on behalf of School of Medicine